(4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazin-3-yl)methyl acetate | 1575612-62-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazin-3-yl)methyl acetate
• 英文别名: 4,5,6,7-Tetrahydrotriazolo[1,5-a]pyrazin-3-ylmethyl acetate
• CAS: 1575612-62-2
• 化学式: C₈H₁₂N₄O₂
• 分子量: 196.209
• InChiKey: BLTZEOBLSFPDSE-UHFFFAOYSA-N

物化性质

• 沸点：
  357.6±52.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazin-3-yl)methyl acetate 在 lithium hydroxide monohydrate 、 碘 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 8.0h， 生成 3-(2,2,2-trifluoroethyl)-5-boc-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine-3-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationship Studies of Novel Fused Heterocycles-Linked Triazoles with Good Activity and Water Solubility

  摘要：

  Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4]-triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.

  DOI：

  10.1021/jm4016284
• 作为产物：
  描述：

  1-acetoxy-4-chloro-but-2-yne 在 吡啶 、 氯化亚砜 、 氢气 、 palladium(II) hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 16.0h， 生成 (4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazin-3-yl)methyl acetate
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationship Studies of Novel Fused Heterocycles-Linked Triazoles with Good Activity and Water Solubility

  摘要：

  Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4]-triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.

  DOI：

  10.1021/jm4016284

文献信息

• PIPERAZINE HETEROARYL DERIVATIVE, PREPARATION METHOD THEREFOR AND USE OF SAME IN MEDICINE
  申请人：JIANGSU HENGRUI MEDICINE CO., LTD.

  公开号：US20200157111A1

  公开（公告）日：2020-05-21

  The present invention relates to a piperazine heteroaryl derivative, a preparation method therefor and the use of same in medicine. In particular, the present invention relates to the piperazine heteroaryl derivative as shown in the general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and the use of same as a capsid protein inhibitor, in particular in the prevention and/or treatment of diseases such as hepatitis B, influenza, herpes, AIDS, etc. The definitions of each group in the general formula (I) are the same as those defined in the description.

  本发明涉及一种哌嗪杂环芳基衍生物，其制备方法以及在医学上的用途。具体来说，本发明涉及如通用式（I）所示的哌嗪杂环芳基衍生物，其制备方法，包括该衍生物的药物组合物，以及将其用作壳蛋白抑制剂，特别是在预防和/或治疗乙型肝炎、流感、疱疹、艾滋病等疾病方面。通用式（I）中每个基团的定义与描述中定义的相同。
• Piperazine heteroaryl derivative, preparation method therefor and use of same in medicine
  申请人：JIANGSU HENGRUI MEDICINE CO., LTD.

  公开号：US11247998B2

  公开（公告）日：2022-02-15

  The present invention relates to a piperazine heteroaryl derivative, a preparation method therefor and the use of same in medicine. In particular, the present invention relates to the piperazine heteroaryl derivative as shown in the general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and the use of same as a capsid protein inhibitor, in particular in the prevention and/or treatment of diseases such as hepatitis B, influenza, herpes, AIDS, etc. The definitions of each group in the general formula (I) are the same as those defined in the description.

  本发明涉及一种哌嗪杂芳基衍生物、其制备方法及其在医药中的用途。特别是，本发明涉及通式（I）所示的哌嗪杂芳基衍生物、其制备方法、包含该衍生物的药物组合物，以及其作为囊壳蛋白抑制剂的用途，尤其是在乙型肝炎、流感、疱疹、艾滋病等疾病的预防和/或治疗中的用途。通式（I）中各基团的定义与描述中的定义相同。
• [EN] PIPERAZINE HETEROARYL DERIVATIVE, PREPARATION METHOD THEREFOR AND USE OF SAME IN MEDICINE<br/>[FR] DÉRIVÉ DE PIPÉRAZINE HÉTÉROARYLE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION EN MÉDECINE<br/>[ZH] 哌嗪并杂芳基类衍生物、其制备方法及其在医药上的应用
  申请人：JIANGSU HENGRUI MEDICINE CO

  公开号：WO2019020070A1

  公开（公告）日：2019-01-31

  本发明涉及哌嗪并杂芳基类衍生物、其制备方法及其在医药上的应用。特别地，本发明涉及通式(I)所示的哌嗪并杂芳基类衍生物、其制备方法、含有该衍生物的药物组合物，以及其作为衣壳蛋白抑制剂，特别是在预防和/或治疗乙型肝炎、流感、疱疹和艾滋病等疾病中的用途。其中通式(I)中的各基团的定义与说明书中的定义相同。